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Infection and Immunity, April 1999, p. 1887-1893, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of Gamma Interferon in Cellular Immune Response against Murine Encephalitozoon cuniculi Infection

Imtiaz A. Khan,* and Magali Moretto

Department of Medicine and Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756

Received 14 September 1998/Returned for modification 28 October 1998/Accepted 8 January 1999

Microsporidia are obligate intracellular protozoan parasites that cause a wide variety of opportunistic infection in patients with AIDS. Because it is able to grow in vitro, Encephalitozoon cuniculi is currently the best-studied microsporidian. T cells mediate protective immunity against this parasite. Splenocytes obtained from infected mice proliferate in vitro in response to irradiated parasites. A transient state of hyporesponsiveness to parasite antigen and mitogen was observed at day 17 postinfection. This downregulatory response could be partially reversed by addition of nitric oxide (NO) antagonist to the culture. Mice infected with E. cuniculi secrete significant levels of gamma interferon (IFN-gamma ). Treatment with antibody to IFN-gamma or interleukin-2 (IL-12) was able to neutralize the resistance to the parasite. Mutant animals lacking the IFN-gamma or IL-12 gene were highly susceptible to infection. However, mice unable to secrete NO withstood high doses of parasite challenge, similar to normal wild-type animals. These studies describe an IFN-gamma -mediated protection against E. cuniculi infection that is independent of NO production.


* Corresponding author. Mailing address: Department of Medicine and Microbiology, HB 7506, Dartmouth Medical School, Lebanon, NH 03756. Phone: (603) 650-8706. Fax: (603) 650-6841. E-mail: Imtiaz.Khan{at}dartmouth.edu.


Infection and Immunity, April 1999, p. 1887-1893, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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